BIOORGANIC CHEMISTRY
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2022
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IF 5.307
Chuansheng Yao,Xiaoying Jiang,Rui Zhao,Zhichao Zhong,Jiamin Ge,Junlong Zhu,Xiang-Yang Ye,Yuanyuan Xie,Zhen Liu,Tian Xie,Renren Bai
A series of N -propargylamine-hydroxamic acid/ o -aminobenzamide hybrids inhibitors combining the typical pharmacophores of hydroxamic acid/o-aminobenzamide and propargylamine were designed and synthesized as HDAC1/MAO-B dual inhibitors for the treatment of Alzheimer’s disease. Most of the hybrids displayed moderate to good MAO-B inhibitory activities. Among them, Hybrid If exhibited the most potent activity against MAO-B and HDAC1 (MAO-B, IC 50 = 99.0 nM; HDAC1, IC 50 = 21.4 nM) and excellent MAO selectively (MAO-A, IC 50 = 9923.0 nM; SI = 100.2). Moreover, compound If significantly reversed Aβ1-42-induced PC12 cell damage and decreased the production of intracellular ROS, exhibiting favorable antioxidant activity. More importantly, hybrid If instantly penetrated the BBB and accumulated in brain tissue as well as markedly ameliorated cognitive dysfunction in a Morris water maze ICR mice model. In summary, HDAC1/MAO-B dual inhibitor If is a promising potential agent for the therapy of Alzheimer’s disease.
研究领域:
神经生物学
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药物化学
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医学
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高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2026
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IF 4.8
Chenchen Wang,Xiaolei Song,Diantao Chen,Junyu Su,Yong Wang,Cheng Huang,Wei Wei
Considering the irreversible nature of Alzheimer's disease (AD), early diagnosis is of great importance for AD treatment. Both β-amyloid (Aβ) and monoamine oxidase B (MAO-B) are potential biomarkers for AD. This study developed a surface-enhanced Raman scattering (SERS) sensor using gold-nanocube (OX-AuNCs) to detect Aβ42 and MAO-B. OX-AuNCs, a type of gold-nanocube with open gaps, achieved a Raman enhancement factor of 8.99 × 10 8 due to numerous hot spots. The specific affinity between Thioflavin T (ThT) and Aβ42 inhibits ThT's intramolecular rotation, reducing its SERS signal. This reduced signal showed a linear correlation with Aβ42 concentrations from 66.70 pM to 0.20 μM, achieving a limit of detection (LOD) at 44.30 pM, while also distinguishing different aggregation levels of Aβ42. Interestingly, SERS intensity of phenethylamine (PEA) also decreased significantly when interacting with MAO-B. A linear relationship was found between the change in PEA intensity and MAO-B concentration (0.01–20.00 μg mL −1 ), yielding an LOD of 5.00 ng mL −1 . The proposed SERS sensor effectively detected two potential AD biomarkers, Aβ42 and MAO-B, in artificial cerebrospinal fluid (ACSF) and human serum with satisfactory recovery rates, respectively. These results show promise for clinical diagnosis and drug screening for AD.
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高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Yunfei Tang,Mengmeng Xiao,Tongtong Duo,Xiaowan Zhang,Ziyue Chen,Wei Wei
The abnormal expression of monoamine oxidase B (MAO-B) and the soluble oligomer (Aβo) formed by β-amyloid deposition play key roles in the pathogenesis of Alzheimer’s disease. However, the simultaneous detection of MAO-B and Aβo remains a huge challenge. Herein, a bimetallic core–shell probe ZIF-8 embedding rhodamine 6G (Au/Rh6G/Pd@ZIF-8) with peroxidase-like activity is designed to detect MAO-B and Aβo simultaneously. MAO-B catalyzes the substrate phenethylamine (PEA) to produce H2O2, which oxidizes thiamine with the catalysis of Au/Rh6G/Pd@ZIF-8 to produce a fluorescent product that emits a strong fluorescence at 440 nm. When Aβo is present in the system, due to the specific coordination between Aβo and Zn2+, the intact ZIF-8 structure collapses, leading to Rh6G release and fluorescence recovery. The simultaneous determination of MAO-B and Aβo by Au/Rh6G/Pd@ZIF-8 is realized. The results showed that the designed biosensor had high specificity and sensitivity, a wide detection range, and a low detection limit for MAO-B and Aβo simultaneous detection. Fluorescence signals for MAO-B and Aβo detection did not interfere with each other because they are excited separately, which provides more valuable data for the diagnosis of Alzheimer’s disease.
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BIOORGANIC CHEMISTRY
·
2018
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IF 3.929
Qi He,Jing Liu,Jin-Shuai Lan,Jiaoli Ding,Yongbing Sun,Yuanying Fang,Neng Jiang,Zunhua Yang,Liyuan Sun,Yi Jin,Sai-Sai Xie
A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer’s disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC 50 values of 0.0068 μM and 0.0089 μM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114 µM for hAChE; 0.101 µM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500 mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
研究领域:
药理学
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神经科学
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药物化学
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PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2026
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IF 5.3
Wei Li,Yan Guo,Xiaoli Wang,Chunyan Yang,Jiang Zhu,Zhongcheng Cao
Alzheimer’s disease (AD) still lacks therapies that definitively halt its progression. Dual AChE/MAO-B inhibitors offer a promising strategy to address both symptoms and pathology. Here, we designed and synthesised a series of donepezil-safinamide hybrids. The optimised compound 28c was identified as a potent inhibitor of AChE (IC50 = 1.70 μM) and MAO-B (IC50 = 0.18 μM). Mechanistic studies indicated that 28c acts as a reversible mixed-type inhibitor of AChE and a competitive reversible inhibitor of MAO-B. Molecular docking and molecular dynamic simulations revealed that 28c could strongly and stably bind to MAO-B and AChE mainly through van der Waals interactions. Moreover, compound 28c demonstrated effective blood-brain barrier penetration, exhibited suitable stability in mouse plasma and brain homogenate, and showed a favourable safety profile both in vitro and in vivo. Furthermore, 28c could attenuate AD-related symptoms and exert hippocampal neuroprotection effect in vivo, highlighting its promise as an anti-AD candidate.
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高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
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2020
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IF 3.073
Xiaoying Jiang,Jianan Guo,Yangjing Lv,Chuansheng Yao,Changjun Zhang,Zhisheng Mi,Yuan Shi,Jinping Gu,Tao Zhou,Renren Bai,Yuanyuan Xie
A series of (3-hydroxypyridin-4-one)-coumarin hybrids were developed and investigated as potential multitargeting candidates for the treatment of Alzheimer's disease (AD) through the incorporation of iron-chelating and monoamine oxidase B (MAO-B) inhibition. This combination endowed the hybrids with good capacity to inhibit MAO-B as well as excellent iron-chelating effects. The pFe 3+ values of the compounds were ranging from 16.91 to 20.16, comparable to more potent than the reference drug deferiprone (DFP). Among them, compound 18d exhibited the most promising activity against MAO-B, with an IC 50 value of 87.9 nM. Moreover, compound 18d exerted favorable antioxidant activity, significantly reversed the amyloid- β 1-42 (A β 1-42 ) induced PC12 cell damage. More importantly, 18d remarkably ameliorated the cognitive dysfunction in a scopolamine-induced mice AD model. In brief, a series of hybrids with potential anti-AD effect were successfully obtained, indicating that the design of iron chelators with MAO-B inhibitory and antioxidant activities is an attractive strategy against AD progression.
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高影响因子
ACTA CHIMICA SLOVENICA
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2017
·Vol. 64
·期 4
·825-831
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IF 0.983
Ren YJ,Zhu JL,Zhang LX,Xu YX,Qian SS.
Three new complexes derived from 2-(4-(pyridin-2-yl)piperazin-1-yl)acetic acid (HL), [M(L)2(H2O)2] where M = CuII (1), ZnII (2) and CdII (3), have been synthesized and characterized by IR spectroscopy, elemental analysis and X-ray crystallography. The inhibitory activity of these three complexes against MAO-B was tested in vitro, and the molecular docking experiments were also carried out to rationalize their binding models. Both the experimental and docking simulation results indicated that complex 1 has the best inhibitory activity with IC50 value being 6.5 ± 0.31 μM.
研究领域:
无机化学
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药物化学
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生物无机化学
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神经药理学
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结构化学
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高影响因子
危险品化学品经营许可证（带存储）